The synthesis of Metoprolol base was studied using Raman spectroscopy with
a 785-nm laser, optical fibres, a holographic transmission grating, confoca
l optics and a charge-coupled device (CCD) detector. The reaction mixture w
as heated according to a temperature gradient and spectra of the reaction m
ixture were obtained by focusing the laser beam through ordinary reaction f
lasks. Because of overlapping bands, multivariate techniques such as princi
pal components analysis (PCA) and partial least-squares projections to late
nt structures (PLS) were used in the evaluation of the obtained spectra. Th
e use of PCA or PLS against, time does not require any calibration samples
and a quantitative calibration is not necessary in order to monitor the rea
ction. A method for reaction endpoint determination, based on euclidean dis
tances in the score space, is presented. The use of multivariate batch cont
rol charts have been demonstrated and a number of problems and solutions re
garding the sample presentation have been discussed. The effect of spectral
pretreatment on the multivariate results is shown and discussed. The monit
oring results show that the time to produce Metoprolol base could be reduce
d. (C) 2000 Elsevier Science B.V. All rights reserved.